That international constellation of people and places — and fish – are the touch points in a study that may lead to a better way to detect Parkinson’s disease. Connecting the dots was a Van Andel Institute scientist named Sok Kean Khoo, who scanned and analyzed blood samples in a bright, glass-roofed lab overlooking downtown Grand Rapids.

From Malaysia to Michigan

Khoo, who is of Chinese descent and grew up in Malaysia, has worked at VAI for 13 years. Although she was initially involved in cancer research, she noticed Parkinson’s patients’ blood samples stored in a freezer at the institute. She wondered if she could apply a cancer research technique, looking for tiny molecules called microRNA, to investigate a neurodegenerative disease.

Her pilot project, published in December in the Journal of Parkinson’s Disease, was the first to identify a molecular biomarker in blood plasma that may one day be used to develop a blood test for Parkinson’s.

Ultimately, Khoo hopes the research will lead to treatments targeting genes that cause the disease, preventing its steady degeneration of the central nervous system.

“But one step at a time,” she said. “My closest goal is to find a diagnostic test.”

“A diagnostic test to determine the status of a patient’s disease onset would provide crucial data for more timely, efficient and successful therapeutic interventions,” said Dr. Patrik Brundin, the director of VAI’s Center for Neurodegenerative Science. “Dr. Khoo’s interesting study is an important step in that direction.”

In Parkinson’s disease, nerve cells in the brain that make dopamine are destroyed. This disrupts nerve cell communication and leads to loss of muscle function. Current diagnosis of the disease is based on a doctor’s clinical observation of symptoms such as rigidity, tremors and difficulty with movement or walking.

“By the time you have all those motor symptoms, your neuron that releases dopamine is already degenerated,” Khoo said. “You actually are in the later stage or your Parkinson’s.”

Also, she said, the diagnosis is challenging because it is subjective and because other diseases mimic Parkinson’s symptoms.

FACT BOX

Parkinson’s disease is the second most common degenerative disorder of the central nervous system.

• About 60,000 new cases diagnosed each year in the U.S.
• Symptoms include tremors, rigidity, slowness of movement and impaired balance
• Affects 1½ times more men than women

“The ultimate aim is to find a way to detect Parkinson’s disease in earlier stages, quantifiably,” she said.

Patients would welcome an accurate test to confirm a clinical diagnosis of Parkinson’s, said Dr. Leslie Neuman, a neurologist at Saint Mary’s and collaborator on the study.

“A sensitive and reliable biomarker would be invaluable to the diagnostic process, especially as we get into the areas of disease modification and neuroprotection,” he said.

Khoo said she chose to look for markers in the blood, rather than in spinal fluid or brain scans, because a blood test is less invasive, quicker and less expensive than MRIs and spinal fluid tests.

Lessons from rainbow trout

Khoo’s study drew on doctorate research she performed in Japan on rainbow trout. Her aim then was to use biomarker-selective breeding to produce disease-resistant fish.

In 2000, Khoo came to VAI to do postdoctoral research, applying her knowledge of biomarkers as she studied kidney cancer. But the institute, started by Amway co-founder Jay Van Andel, who died of Parkinson’s, also has a strong focus on Parkinson’s research.

The generosity of Grand Rapids patients

About three years ago, she became intrigued by 100 blood samples of Parkinson’s patients stored in a freezer for research. The samples were donated between 2005 and 2009 by Parkinson’s patients in the Hauenstein Neuroscience Center at Saint Mary’s. For a control group, another 100 samples were donated by people who didn’t have the disease – in most cases, the spouses of the patient.

The donations reflected the depth of community support in Grand Rapids, Khoo said. At conferences, colleagues tell her such generosity with samples is uncommon in big cities.

Michael J. Fox Foundation funds pilot project

She proposed looking for a plasma biomarker for Parkinson’s in the blood samples. She applied for a “small grant” from the Michael J. Fox Foundation, an organization formed by the actor who has Parkinson’s disease. She received a $70,000 Rapid Response Innovation Award.

“Nobody thought I’d get it because I have an oncology background,” Khoo said. “It was amazing I got it.”

The funds were enough to test her concept with 32 blood samples to see if it was worth pursuing.

“We are looking for a small molecule called a microRNA,” she said. “It is about 17 to 22 nucleotides.”

The tiny molecule, which is involved in regulating RNA, has become a popular target for cancer research in the past five years, she said.

“It is very small, but surprisingly it is very, very stable,” Khoo said. “Yet, it is abundant, and it is very tissue-specific.”

She ran slides of blood samples through a micro array scanner, a device encapsulated in a large ozone-free box to protect the fluorescent dyes used to mark the results. For each scan, it produced a pattern of red, green and black squares, which indicated the amount of gene expression in the microRNA.

She compared the colorful scans of the blood samples and found a panel of four microRNA that was distinctive to the Parkinson’s patients.

The link to Sweden

Before she could publish her findings, Khoo had to duplicate the results with another group of patients. She was able to secure samples from Sweden — Brundin, the director of neurodegenerative disease research, came to VAI from Lund University in Sweden.

However, money was an issue. Her grant from the Fox Foundation was running out.

Rockford basketball coach inspires donations

That’s when Brundin suggested she tap funds raised on behalf of Steve Majerle, a former Rockford High School teacher and basketball coach. After Majerle was forced to retire in 2011 because of Parkinson’s disease, friends and fans donated $16,000 to VAI for Parkinson’s research.

Learning the donations played a vital role in Khoo’s study is “awesome,” Majerle said. “It’s good to know the money went to good use.”

Since retiring, he has undergone a deep brain stimulation treatment that has controlled the tremors and other symptoms so well, he has been able to return to work part-time. He now coaches basketball for Grand Rapids Christian High School.

The treatment has dramatically improved his life, but it’s not a cure. He hopes it will buy him time until scientists can discover a way to halt or reverse the damage caused by Parkinson's.

What’s next

The next step for Khoo’s research is to conduct a new study with 120 Parkinson’s patients. She is applying for a $500,000 grant from the National Institutes of Health. If the concept holds up, she will expand the research to multiple clinic sites.

Eventually, if all goes well, she hopes microRNA could be used to create a targeted gene therapy for Parkinson’s.

“This will be in the future,” she cautioned. “I cannot promise you when. But I think we are doing the right thing moving that forward.”

Khoo said she is grateful to the patients who provided the blood samples that sparked the first phase of her research. To them, she said simply, “A very big thank you.”